External cephalic version in nonvertex second twin-Success rate, mode of delivery, and safety: A systematic review.

Introduction: One of the key challenges regarding the management of twins involves choosing the optimal mode of delivery, which is strongly influenced by the final presentation of both fetuses. In cases of vertex-nonvertex pregnancies attempting the trial of vaginal delivery, external cephalic version (ECV) is one of possible management options. The main objective of this review was to collect and summarize available data in terms of the application of ECV in the population of nonvertex second twins.

Culture Shock: An Investigation into the Tolerance of Pathogenic Biofilms to Antiseptics in Environments Resembling the Chronic Wound Milieu.

Credible assessment methods must be applied to evaluate antiseptics' in vitro activity reliably. Studies indicate that the medium for biofilm culturing should resemble the conditions present at the site of infection. We cultured , , , , and biofilms in IVWM (In Vitro Wound Milieu)-the medium reflecting wound milieu-and were compared to the ones cultured in the laboratory microbiological Mueller-Hinton (MH) medium.

The Role of Soy Isoflavones in the Prevention of Bone Loss in Postmenopausal Women: A Systematic Review with Meta-Analysis of Randomized Controlled Trials.

The aim of the report was to determine the effects of soy isoflavones on lumbar spine, femoral neck, and total hip bone mineral density (BMD) in menopausal women. MEDLINE (PubMed), EMBASE, and Cochrane Library databases were searched for articles published in English during 1995-2019. Studies were identified and reviewed for inclusion and exclusion eligibility.

Small extracellular vesicles containing arginase-1 suppress T-cell responses and promote tumor growth in ovarian carcinoma.

Tumor-driven immune suppression is a major barrier to successful immunotherapy in ovarian carcinomas (OvCa). Among various mechanisms responsible for immune suppression, arginase-1 (ARG1)-carrying small extracellular vesicles (EVs) emerge as important contributors to tumor growth and tumor escape from the host immune system. Here, we report that small EVs found in the ascites and plasma of OvCa patients contain ARG1.

Biological markers of prognosis, response to therapy and outcome in ovarian carcinoma.

Introduction: Ovarian cancer (OvCa) is among the most common types of cancer and is the leading cause of death from gynecological malignancies in western countries. Cancer biomarkers have a potential for improving the management of OvCa patients at every point from screening and detection, diagnosis, prognosis, follow up, response to therapy and outcome.

Areas Covered: The literature search has indicated a number of candidate biomarkers have recently emerged that could facilitate the molecular definition of OvCa, providing information about prognosis and predicting response to therapy.

Antagonism of tumoral prolactin receptor promotes autophagy-related cell death.

Therapeutic upregulation of macroautophagy in cancer cells provides an alternative mechanism for cell death. Prolactin (PRL) and its receptor (PRLR) are considered attractive therapeutic targets because of their roles as growth factors in tumor growth and progression. We utilized G129R, an antagonist peptide of PRL, to block activity of the tumoral PRL/PRLR axis, which resulted in inhibition of tumor growth in orthotopic models of human ovarian cancer.

Exosomes in Plasma of Patients with Ovarian Carcinoma: Potential Biomarkers of Tumor Progression and Response to Therapy.

Background: In patients with Ovarian Cancer (OvCa) exosomes released by tumor cells are present in the plasma and could be involved in tumor progression. This study examines the association between the exosome presence/protein content in plasma of OvCa patients and disease outcome, response to standard therapy and/or tumorresistance to therapies in patients studied at diagnosis and also serially during and after therapy.

Design And Methods: Exosomes were purified from OvCa patients' plasma (n=22), patients with benign tumors (n=10) or (n=10) healthy controls (NC) using ultracentrifugation.

17β Hydroxysteroid dehydrogenase type 12 (HSD17B12) is a marker of poor prognosis in ovarian carcinoma.

Objective: 17β-hydroxysteroid dehydrogenase isoform 12 (HSD17B12) overexpression is associated with poor clinical outcome in invasive ductal carcinoma of the breast. Here, we evaluated HSD17B12 overexpression and its activity in ovarian carcinoma (OvCa) to determine its role in the growth and progression of this tumor.

Methods: Immunohistochemical analysis of HSD17B12 expression was performed in 100 tissue samples of untreated OvCa and was correlated with clinicopathologic characteristics and patient outcome.

A gynecologic oncology group phase II trial of two p53 peptide vaccine approaches: subcutaneous injection and intravenous pulsed dendritic cells in high recurrence risk ovarian cancer patients.

Purpose: Peptide antigens have been administered by different approaches as cancer vaccine therapy, including direct injection or pulsed onto dendritic cells; however, the optimal delivery method is still debatable. In this study, we describe the immune response elicited by two vaccine approaches using the wild-type (wt) p53 vaccine.

Experimental Design: Twenty-one HLA-A2.

Blast-derived microvesicles in sera from patients with acute myeloid leukemia suppress natural killer cell function via membrane-associated transforming growth factor-beta1.

Background: Natural killer cell cytotoxicity is decreased in patients with acute myeloid leukemia in comparison to that in normal controls. Tumor-derived microvesicles present in patients' sera exert detrimental effects on immune cells and may influence tumor progression.

Design And Methods: We investigated the microvesicle protein level, molecular profile and suppression of natural killer cell activity in patients with newly diagnosed acute myeloid leukemia.

Mechanisms of tumor escape from the immune system: adenosine-producing Treg, exosomes and tumor-associated TLRs.

Human tumors utilize many different mechanisms of immunosuppression to prevent immune cells from exercising their antitumor activities. These mechanisms, which enable the tumor to escape from the host immune system and to progress, are being intensively investigated in hope of finding therapeutically safe and effective inhibitors able to counteract tumor-induced immunosuppression. Three of more recently discovered tumor-related suppression mechanisms, i.

Mechanisms of T-cell protection from death by IRX-2: a new immunotherapeutic.

Objectives: IRX-2 is a novel immunotherapeutic containing physiologic quantities of several cytokines which protects human T lymphocytes from tumor-induced or drug-induced apoptosis. Here, we investigate the mechanisms responsible for IRX-2-mediated protection of T lymphocytes exposed to tumor-derived microvesicles (TMV).

Methods: Jurkat cells or primary human T cells ± IRX-2 were co-incubated with TMV and then examined by flow cytometry or Western blots for expression of molecules regulating cell survival (FLIP, Bcl-2, Bcl-xL, Mcl-1) or death (Fas, caspase 8, caspase 9, Bax, Bid).

[Expression of survivin, SDF-1 and CXCR4 on tumor cells in ovarian cancer].

Background: epithelial ovarian cancer (EOC) has the highest mortality rate among patients with gynecologic malignancies. Lack of specific and early symptoms and of screening tests causes that most patients are diagnosed in advanced stage of disease. Radical surgery followed by chemotherapy does not bring satisfactory curative effects.

Tumor-derived microvesicles induce, expand and up-regulate biological activities of human regulatory T cells (Treg).

Background: Tumor-derived microvesicles (TMV) or exosomes are present in body fluids of patients with cancer and might be involved in tumor progression. The frequency and suppressor functions of peripheral blood CD4(+)CD25(high)FOXP3(+) Treg are higher in patients with cancer than normal controls. The hypothesis is tested that TMV contribute to induction/expansion/and activation of human Treg.

Adenosine and prostaglandin E2 cooperate in the suppression of immune responses mediated by adaptive regulatory T cells.

Adaptive regulatory T cells (Tr1) are induced in the periphery upon encountering cognate antigens. In cancer, their frequency is increased; however, Tr1-mediated suppression mechanisms are not yet defined. Here, we evaluate the simultaneous involvement of ectonucleotidases (CD39/CD73) and cyclooxygenase 2 (COX-2) in Tr1-mediated suppression.

Regulatory T cell suppression of Gag-specific CD8 T cell polyfunctional response after therapeutic vaccination of HIV-1-infected patients on ART.

We tested the hypothesis that therapeutic vaccination against HIV-1 can increase the frequency and suppressive function of regulatory, CD4(+) T cells (Treg), thereby masking enhancement of HIV-1-specific CD8(+) T cell response. HIV-1-infected subjects on antiretroviral therapy (N = 17) enrolled in a phase I therapeutic vaccine trial received 2 doses of autologous dendritic cells (DC) loaded with HIV-1 peptides. The frequency of CD4(+)CD25(hi)FOXP3(+) Treg in blood was determined prior to and after vaccination in subjects and normal controls.

Reciprocal granzyme/perforin-mediated death of human regulatory and responder T cells is regulated by interleukin-2 (IL-2).

Human CD4(+)CD25(high)FOXP3(+) T regulatory cells (Treg) can suppress responder T cell (RC) functions by various mechanisms. In co-cultures of Treg and autologous activated RC, both cell subsets up-regulate the expression of granzymes and perforin, which might contribute to Treg-mediated suppression. Here, we investigate the sensitivity and resistance of Treg and RC to granzyme/perforin-mediated death.

Generation and accumulation of immunosuppressive adenosine by human CD4+CD25highFOXP3+ regulatory T cells.

Naturally occurring regulatory T cells (nTreg) are crucial for maintaining tolerance to self and thus preventing autoimmune diseases and allograft rejections. In cancer, Treg down-regulate antitumor responses by several distinct mechanisms. This study analyzes the role the adenosinergic pathway plays in suppressive activities of human nTreg.

TLR4 signaling induced by lipopolysaccharide or paclitaxel regulates tumor survival and chemoresistance in ovarian cancer.

Toll-like receptors (TLRs) expressed on immune cells trigger inflammatory responses. TLRs are also expressed on ovarian cancer (OvCa) cells, but the consequences of signaling by the TLR4/MyD88 pathway in these cells are unclear. Here, TLR4 and MyD88 expression in OvCa tissues (n=20) and cell lines (OVCAR3, SKOV3, AD10, A2780 and CP70) was evaluated by reverse transcriptase-PCR, western blots and immunohistochemistry.

Increased ectonucleotidase expression and activity in regulatory T cells of patients with head and neck cancer.

Purpose: Regulatory T cell (Treg) frequency and activity are increased in cancer patients and play a major role in tumor escape. Although disease progression is favored by the presence of Treg, mechanisms used by Treg to suppress antitumor immunity are unknown. The ectonucleotidases CD39 and CD73 are expressed in Treg and convert ATP into immunosuppressive adenosine.

Tumor-derived microvesicles promote regulatory T cell expansion and induce apoptosis in tumor-reactive activated CD8+ T lymphocytes.

Sera of patients with cancer contain membraneous microvesicles (MV) able to induce apoptosis of activated T cells by activating the Fas/Fas ligand pathway. However, the cellular origin of MV found in cancer patients' sera varies as do their molecular and cellular profiles. To distinguish tumor-derived MV in cancer patients' sera, we used MAGE 3/6(+) present in tumors and MV.

Differential responses of human regulatory T cells (Treg) and effector T cells to rapamycin.

Background: The immunosuppressive drug rapamycin (RAPA) promotes the expansion of CD4(+) CD25(high)Foxp3(+) regulatory T cells via mechanisms that remain unknown. Here, we studied expansion, IL-2R-gamma chain signaling, survival pathways and resistance to apoptosis in human Treg responding to RAPA.

Methodology/principal Findings: CD4(+)CD25(+) and CD4(+)CD25(neg) T cells were isolated from PBMC of normal controls (n = 21) using AutoMACS.

Interleukin-15 enhances natural killer cell cytotoxicity in patients with acute myeloid leukemia by upregulating the activating NK cell receptors.

Interleukin-15 (IL-15) has a major role in NK-cell homeostasis. Modulation of the relative frequency and expression intensity of the NK-cell receptors by IL-15 may increase NK cell-mediated cytotoxicity in cancer patients. We investigated the receptor repertoire and measured NK-cell activity in newly diagnosed AML patients and evaluated the ex vivo effects of IL-15.

Biological significance of prolactin in gynecologic cancers.

There is increasing evidence that prolactin (PRL), a hormone/cytokine, plays a role in breast, prostate, and colorectal cancers via local production or accumulation. Elevated levels of serum PRL in ovarian and endometrial cancers have been reported, indicating a potential role for PRL in endometrial and ovarian carcinogenesis. In this study, we show that serum PRL levels are significantly elevated in women with a strong family history of ovarian cancer.

Increased frequency and suppression by regulatory T cells in patients with acute myelogenous leukemia.

Purpose: Regulatory CD4(+)CD25(high)Foxp3(+) T cells (Treg) control peripheral immune tolerance. Patients with cancer, including those with hematologic malignancies, have elevated numbers of Treg in the peripheral circulation and in tumor tissues. However, mechanisms of suppression and clinical significance of Treg, especially in patients with acute myelogenous leukemia (AML), has not been well defined.